Work will continue on the separation of the water soluble substance, which appears to a high carbohydrate containing glycoprotein, responsible for the intense IOP lowering activity of aqueous extracts of Cannabis sativa. Good success has been realized with gel filtration resins such as Sephacryl S-200. Emphasis will be placed on developing ion exchange (such as diethylaminoethyl cellulose) and affinity chromatography (such as concanavalin A - agarose) leads. Analysis of these fractions will be done in part by gel electrophoresis and isoelectric focusing, once good conditions for separation of the glycoproteins have been developed. A pure active material is available, the major effort will then be shifted to the chemical and physical characterization of this material. Precise analysis of molecular weight, number and type of sugars and amino acids, branching and linkage between carbohydrate and protein will be made by standard chemical, spectroscopic, chromatographic (including MS/GC) and 13C NMR studies. Chemical and biological transformations of the active material will also be made in order to study its structural features, understand which portions of the molecular are necessary for activity and to aid in the understanding of its mechanism of action. These will include enzymatic as well as selected chemical degradations, as well as lakellin, with radioactive and optical markers. Other plants will also be screened for IOP lowering activity. In addition some synthetic cannabinoids will be made and screened for IOP lowering activity.